Case 5
Helmut Hopfer
Institute of Pathology, University Hospital Basel
Morphological features
• Intratubular crystals of needle-shaped to
rectangular aggregates
• Brownish colour in PAS and HE stains
• Birefringence
• Von Kossa stain negative
• Giant cells
• Interstitial fibrosis and tubular atrophy
Clinical history
• Subacute renal failure, serum creatinine
1250 umol/l (14.1 mg/dl)
• Known autosomal dominant polycystic
kidney disease since childhood
• Microhematuria, minimal proteinuria
• Hypertension
• 2 episodes of renal colics, three and two
years prior to admission, radiolucent
stones on X-rays
Differential diagnosis
Nephrocalcinosis
Oxalosis
Urate nephropathy
Cystinosis
Drug-induced crystals
2,8-Dihydroxyadenine urolithiasis
2,8-DHA urolithiasis
• Autosomal recessive inherited adenine
phosphoribosyltransferase deficiency
(APRT), homozygosity rate 1:50'000100'000
• Recurrent urolithiasis
♂
♀
• APRT deficient
(heterozygous)
• APRT deficient
(heterozygous)
• ADPKD
♂
♂
• APRT deficient
(homozygous)
• ADPKD
• APRT deficient
(heterozygous)
♀
• APRT normal
• ADPKD
2,8-DHA urolithiasis
Adeninemonophosphate
Adenine
APRT
XO
8-Hydroxyadenine
XO
2,8-Dihydroxyadenine
APRT – Adenine phosphoribosyltransferase
XO – Xanthine oxydase
DNA synthesis
RNA synthesis
Energy transfer
2,8-DHA urolithiasis
Adenine
APRT
mutation
Adeninemonophosphate
XO
8-Hydroxyadenine
XO
2,8-Dihydroxyadenine
 Excretion into the urine
 Formation of crystals at
physiological pH
 Urolithiasis
APRT – Adenine phosphoribosyltransferase
XO – Xanthine oxydase
2,8-DHA urolithiasis
Adenine
APRT
mutation
XO
Adeninemonophosphate
Allopurinol
8-Hydroxyadenine
XO
2,8-Dihydroxyadenine
 Prevention of urolithiasis
APRT – Adenine phosphoribosyltransferase
XO – Xanthine oxydase
2,8-DHA urolithiasis
• Treatment with allopurinol, low purine diet,
high fluid intake
• Clinical DD: urate nephropathy
(radiolucent stones, standard chemical
test does not differentiate)
• Pathological DD: oxalosis (strong
birefringence)
Differential diagnosis
Nephrocalcinosis
Oxalosis
Urate nephropathy
Cystinosis
Drug-induced crystals
2,8-Dihydroxyadenine urolithiasis
Oxalosis
Nephrocalcinosis
Calcium containing crystals
Oxalate nephropathy
Kossa
Alizarin
• Shape: round to elongate,
mostly rhomboid; clusters
or rosette-like
• Location: intraluminal,
below the tubular
epithelium or interstitium
• Colour: transparent,
birefringence in polarized
light (H&E stain)
• Special stains: von Kossa
black, Alizarin orange/red
Urate nephropathy
• Shape: needle shaped to
rectangular aggregates
within an amorphous
matrix
• Location: tophi mostly in
the medulla
• Colour: FFPE biopsies –
mostly dissolved, alcoholfixed biopsies – pale to
deep blue, birefringence in
polarized light
• Special stains: von Kossa
negative, Alizarin negative
Cystinosis
• Shape: brick, hexagonal,
elongated or flat
• Colour: FFPE biopsies –
mostly dissolved, alcoholfixed biopsies – yellow,
brown to sand colour,
birefringence under
polarized light
• Special stains: von Kossa
negative, Alizarin negative
Drug-induced crystals
•
•
•
•
•
•
Sulfonamides
Acyclovir
Methotrexate
Indinavir
Triamterene
...
Perazella MA, Am J Med 106:
459-465, 1999
Sulfonamide crystals (1960's)
2,8-DHA urolithiasis
• Brownish intratubular
crystals
• Strong birefringence
• Giant cells
• Von Kossa negative
→ Think of 2,8-DHA
urolithiasis in all cases
of oxalosis!